[Stratified application of gene expression in diagnosis of thyroid nodules].

Objective: To investigate the value of BRAF V600E and multigene detection and stratified application for the diagnosis of thyroid nodules. Methods: A total of 1 117 patients with thyroid nodules resection at Nanjing Gulou Hospital from December 2020 to July 2022 were enrolled in the study. Fine needle aspiration (FNA) and core biopsy samplings were performed for cytopathologic examination and genetic testings; the findings were combined with BSRTC classification. The diagnostic performance of BRAF V600E and multigene detection were compared. Results: Among the 1, 117 patients who underwent thyroid nodules resection, 285 were male and 832 were female, with a median age of 46 years (range: 24-76 years). Postoperative histopathologic examination confirmed 1 040 cases of thyroid cancer and 77 cases of benign nodules. The sensitivity (87.0% vs. 80.8%, P<0.01) and diagnostic accuracy (87.9% vs. 82.1%, P<0.01) of multigene detection were significantly higher than those of BRAF V600E detection. The result of multigene detection showed that BRAF V600E mutation was the most common finding, followed by CCDC6-RET (E1-E12) fusion, ETV6-NTRK3 fusion, and KRAS mutation. Multigene detection had a higher sensitivity (81.9% vs. 72.8%, P<0.01) and lower cancer risk in wild-type (47.6% vs. 57.7%, P=0.069) than BRAF V600E detection in BSRTCⅠ-Ⅴ lesions. Compared with BRAF V600E detection, multigene had no significant difference of sensitivity in BSRTC Ⅰ lesions, but significantly higher sensitivity (86.3% vs 74.0%, P<0.01) in BSRTC Ⅲ lesions. Conclusions: Genetic detection can be used as an effective tool for the diagnosis of thyroid nodules. A stratified application of molecular markers in the diagnosis of thyroid nodules is proposed. Combined with FNA, single gene or multigene detection both can effectively assist in the diagnosis of thyroid nodules. Moreover, multigene detection is superior to single gene detection. For BSRTC Ⅲ lesion with wild-type BRAF, multigene detection can be considered with a repeated FNA.

[Apatinib Suppressed Macrophage-Mediated Malignant Behavior of Hepatocellular Carcinoma Cells via Modulation of VEGFR2/STAT3/PD-L1 Signaling].

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver tumor worldwide. Tumor-associated macrophages (TAMs) usually have a similar phenotype to M2-like macrophages and can participate in tumor progression by secreting cytokines to suppress the immune response and activity of tumor-infiltrating lymphocytes. We investigated the role of M2 macrophages in HCC progression and explored the effects of vascular endothelial growth factor receptor 2 inhibitor-apatinib. As a cellular model of HCC, Hepb3 cell line was used. M2 macrophages were obtained by differentiation of THP-1 cells. The Transwell chamber was used to co-culture M2 macrophages and Hepb3 cells. CCK-8 and EdU assays were conducted to measure cell viability and proliferation capacity. Transwell migration assay was performed to estimate cellular metastatic potential. Cytokine expression levels were assessed by ELISA. Western blotting was used to characterize activation of the VEGFR2/STAT3/PD-L1 axis. It has been shown that co-culture with M2 macrophages increased viability, cytokine production, promoted proliferation, invasion, and migration of Hepb3 cells. The secretion of TGF-ß1, IL-6, MMP-9, and VEGF was significantly increased after co-culture. In contrast apatinib suppressed M2 macrophage-induced proliferation, cell viability, invasion, and migration of Hepb3 cells. Moreover, apatinib markedly decreased expression levels of p-VEGFR2, p-STAT3, and PD-L1 in Hepb3 cells under the co-culture conditions. In conclusion, apatinib treatment can suppress TAMs-mediated malignant behavior of HCC cells via modulation of the VEGFR2/STAT3/PD-L1 signaling pathway.

Diamond Quantum Sensing Revealing the Relation between Free Radicals and Huntington's Disease.

Huntington's disease (HD) is a well-studied yet rare disease caused by a specific mutation that results in the expression of polyglutamine (PolyQ). The formation of aggregates of PolyQ leads to disease and increases the level of free radicals. However, it is unclear where free radicals are generated and how they impact cells. To address this, a new method called relaxometry was used to perform nanoscale MRI measurements with a subcellular resolution. The method uses a defect in fluorescent nanodiamond (FND) that changes its optical properties based on its magnetic surroundings, allowing for sensitive detection of free radicals. To investigate if radical generation occurs near PolyQ aggregates, stable tetracycline (tet)-inducible HDQ119-EGFP-expressing human embryonic kidney cells (HEK PQ) were used to induce the PolyQ formation and Huntington aggregation. The study found that NDs are highly colocalized with PolyQ aggregates at autolysosomes, and as the amount of PolyQ aggregation increased, so did the production of free radicals, indicating a relationship between PolyQ aggregation and autolysosome dysfunction.

[Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment].

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Plasma poration: Transdermal electric fields, conduction currents, and reactive species transport.

Radical species and electric fields produced by gas plasmas are increasingly used in dermatology. Plasma-poration is the key basis for the efficient plasma skin treatment, which involves the plasma electric field, the directional motion of charged particles, and the transport of reactive particles. However, the enabling mechanisms of the plasma-poration remain unclear and require urgent attention. Here, the plasma-induced electric fields in each skin layer are accurately measured for the first time. The maximum electric field in the stratum corneum is 43 kV/cm, while the electric field in the active epidermis and dermis is about 1.8 kV/cm. This electric field strength is in the range of strength required for electroporation. Different from traditional electroporation treatments, the plasma-poration mainly relies on the effects of strong electric fields and the conductive current. The active power of the plasma-poration up to 18.5 kW/cm3 in the stratum corneum can rapidly change the structure of the skin. At the same time, reactive oxygen and nitrogen species also pass through the stratum corneum and effectively interact with the skin tissue. The plasma-poration does not cause any pain, which is an inevitable side effect of common electroporation.

The association of serum testosterone with dyslipidemia is mediated by obesity: the Henan Rural Cohort Study.

BACKGROUND AND AIMS: This study aimed to evaluate the relationships of serum testosterone with dyslipidemia and blood lipid levels and test whether obesity mediated these associations by gender in Chinese rural population. METHODS AND RESULTS: A total of 6150 subjects were finally analyzed in this study. Serum testosterone for each subject was detected by liquid chromatography equipped with tandem mass spectrometry. Logistic regression and linear regression were employed to evaluate the associations of serum testosterone with the prevalence of dyslipidemia and blood lipid levels. Mediation analysis was conducted to identify the mediation effects of obesity on the relationship between serum testosterone and dyslipidemia. After adjusting for multiple confounders, per unit change in serum ln-testosterone levels was associated with a decreased prevalent dyslipidemia in men (odds ratio (OR): 0.785, 95% confidence interval (CI) (0.708, 0.871)). Males with the levels of serum testosterone in the third or fourth quartiles had a 49.4% (OR: 0.506, 95% CI 0.398, 0.644) or 67.1% (OR: 0.329, 95% CI 0.253, 0.428) significantly lower odds of prevalence of dyslipidemia. In addition, a onefold increase in ln-testosterone was related to a 0.043 mmol/L (95% CI 0.028, 0.059) increase in high-density lipoprotein cholesterol (HDL-C) in men. Results of the mediation analysis suggested that obesity played a partial role in the association of testosterone with dyslipidemia in men. CONCLUSIONS: These findings suggested that serum testosterone levels were negatively associated with lipid levels and prevalent dyslipidemia, and obesity mediated the effects of serum testosterone on dyslipidemia in men, implying that obesity prevention should be highlighted to decrease the prevalence of dyslipidemia related to changes in testosterone levels.

[Microfocal prostate cancer: a clinicopathological analysis of 206 cases].

Objective: To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma. Methods: Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion. Results: A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 µg/L2 versus 23.7 µg/L2; 1.4 µg/L2 versus 3.0 µg/L2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 µg/L2 versus 0.8 µg/L2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions: In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.

[Construction of professional competency model of center for disease prevention and control].

Objective: Analyze and contruct the post competency model of professionals in centers for disease prevention and control in Beijing, so as to provide information for cultivation and construction of public health personnel, and the human Resource Management in relevant institutions. Methods: Cross-sectional research method was used, and based on literature research, functional analysis and referring to Hay Group Competency Dictionary and McClellan Competency Dictionary, the post competency dictionary was established after the unified discussion of the subject group. Hierarchical cluster sampling method was used to investigate an online survey on competency factors of professionals in centers for Disease prevention and Control in Beijing, and factor analysis was conducted on the survey data. Results: The competency model of professionals in centers for disease prevention and control in Beijing was composed of six factors, which are Public health practical operation skills and norms, public health emergency response thinking and deductive and inductive ability, professional quality and professional ethics, communication, coordination ability and team spirit, medicine humanities knowledge and health management and guidance. Conclusions: This competency model is basically in line with the job responsibilities of professionals in centers for disease prevention and control in Beijing. However, it can only reflect the post competence and ability of the middle and junior technical personnel for practice, so which should belongs to the category of basic competence.

Quantum monitoring of cellular metabolic activities in single mitochondria.

Free radicals play a vital role in all kinds of biological processes including immune responses. However, free radicals have short lifetimes and are highly reactive, making them difficult to measure using current methods. Here, we demonstrate that relaxometry measurement, or T1, inherited from the field of diamond magnetometry can be used to detect free radicals in living cells with subcellular resolution. This quantum sensing technique is based on defects in diamond, which convert a magnetic signal into an optical signal, allowing nanoscale magnetic resonance measurements. We functionalized fluorescent nanodiamonds (FNDs) to target single mitochondria within macrophage cells to detect the metabolic activity. In addition, we performed measurements on single isolated mitochondria. We were able to detect free radicals generated by individual mitochondria in either living cells or isolated mitochondria after stimulation or inhibition.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.

Negative associations of morning serum cortisol levels with obesity: the Henan rural cohort study.

AIMS: To evaluate the associations of morning serum cortisol levels with obesity defined by different indices in Chinese rural populations. MATERIALS AND METHODS: A cross-sectional study was performed including 6198 participants (2566 males and 3632 females). Serum cortisol was collected in morning and quantified by liquid chromatography-tandem mass spectrometry. Obesity was defined by body mass index (BMI), body fat percentage (BFP), waist-to-height ratio (WHtR), waist circumference (WC), visceral fat index (VFI) and waist-to-hip ratio (WHR). Both multivariable liner regression, logistic regression and restrictive cubic splines models were used to estimate the gender-specific relationships between cortisol levels and obesity defined by different indices, respectively. RESULTS: After adjusting for potential confounders, serum cortisol was negatively associated with different obesity measures, except obese females defined by BFP (for instance, overall obesity defined by BMI, Quartile 4 vs. Quartile 1, odds ratio (OR) = 0.25, 95% confidence interval (CI):0.15, 0.41 in males, and OR = 0.58, 95% CI: 0.42,0.80 in females, central obesity defined by WC, OR = 0.52, 95% CI:0.39,0.69 in males and OR = 0.63, 95% CI:0.51,0.77 in females). Similarly, restrictive cubic splines showed the nonlinear relationship between high levels of cortisol and different obesity indices. Furthermore, ROC curve analysis indicated that cortisol could improve the discrimination of model with common biomarkers. CONCLUSION: Morning serum cortisol were negatively related to obesity defined by different indices in Chinese rural populations. In addition, cortisol could be as a biomarker for prediction of obesity in males.

LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.

OBJECTIVE: The purpose of this study was to investigate the potential effects of LIM and Src homology 3 (SH3) protein 2 (LASP2) on nasopharyngeal carcinoma (NPC) and the relevant mechanism. PATIENTS AND METHODS: The expression of LASP2 in NPC patients and non-cancer patients in the control group was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The patients were divided into LASP2 high-expression group (n=30) and low-expression group (n=30), according to the median expression level of LASP2. Then, the expression of LASP2 was detected in the chosen cell lines by qRT-PCR. RESULTS: In qRT-PCR experiment, LASP2 was found up-expressed in NPC clinical samples and cell lines. Besides, LASP2 expression was associated with the clinical stage and distant metastasis of NPC. Next, the expression of LASP2 was downregulated by transfection of si-LASP using LipofectamineTM 3000 in 6-10B cells in vitro. The transfection effects of si-LASP2 were confirmed by qRT-PCR and Western-blot (WB) experiments. In supplementary experiments, decreased expression of LASP2 in cells could inhibit the cell biological functions, including invasion, migration, and epithelial-mesenchymal transition (EMT). CONCLUSIONS: This research discovers the promotion effect of LASP2 on NPC, suggesting that LASP2 could be used as a potential therapeutic target for NPC.

[Expression of PD-1, TIM-3, LAG-3 and BTLA in diffuse large B-cell lymphoma and its effect on prognosis].

Objective: To investigate the expression levels of programmed death protein 1 (PD-1)、T cell immunoglobulin domain and mucin domain 3(TIM-3)、lymphocyte activating gene 3 (LAG-3) and B and T lymphocyte attenuator (BTLA) in Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and their effects on prognosis. Methods: The paraffin specimens of 30 patients with DLBCL, NOS newly diagnosed in People's Hospital of Zhengzhou University were stained with immunohistochemistry. The effects of single positive and co-expression of the above molecules on progression-free survival (PFS) phase and overall survival (OS) phase were analyzed. Results: There was no significant difference in prognosis between PD-1, TIM-3, LAG3, BTLA single positive group and single negative group. The median PFS phase of PD-1 and TIM-3 co-expression group and TIM3 and BTLA co-expression group were 26 and 24 months respectively, which were both lower than the 54 months (P=0.021) and 47 months (P=0.037) in non-co-expression group. The median PFS phase and OS phase of PD-1, TIM-3 and LAG-3 co-expression group were 17 and 25 months respectively, which were significantly lower than the 41 months (P=0.024) and 60 months (P=0.015) of non-co-expression group. The median PFS phase and OS phase of PD-1, TIM-3, LAG-3 and BTLA co-expression group were 18 and 26 months respectively, which were significantly lower than the 40 months (P=0.038) and 57 months (P=0.041) of non-co-expression group. Conclusions: In patients with DLBCL, NOS, those with PD-1 and TIM-3 co-expression as well as those with TIM-3 and BTLA co-expression have poor PFS phase. Patients with PD-1, TIM-3 and LAG-3 co-expression and patients with PD-1, TIM-3, LAG-3 and BTLA co-expression have poor PFS and OS phase.

Doppler coherence imaging of scrape-off-layer impurity flows in the HL-2A tokamak.

A new Doppler coherence imaging spectroscopy interferometer has been developed on the HL-2A tokamak for the scrape-off-layer impurity flow measurement. Its spatial resolution is estimated to be up to ∼0.8 mm in the horizontal direction and ∼9 mm in the vertical direction, with a field of view of ∼34°. Its typical temporal resolution is about 1 ms. This salient feature allows for time-resolved 2D measurements in short-time phenomena on HL-2A, such as edge localized modes. Group delay and interference fringe pattern were calibrated with a dedicated calibration system. The robustness of group delay calibration and the feasibility of the extrapolation model for fringe pattern calibration are demonstrated. In this paper, we report the details of the optical instruments, calibration, and the initial experimental results of this Doppler coherence imaging spectroscopy interferometer.

Preformed Cooper Pairs in Layered FeSe-Based Superconductors.

Superconductivity arises from two distinct quantum phenomena: electron pairing and long-range phase coherence. In conventional superconductors, the two quantum phenomena generally take place simultaneously, while in the underdoped high- T_{c} cuprate superconductors, the electron pairing occurs at higher temperature than the long-range phase coherence. Recently, whether electron pairing is also prior to long-range phase coherence in single-layer FeSe film on SrTiO_{3} substrate is under debate. Here, by measuring Knight shift and nuclear spin-lattice relaxation rate, we unambiguously reveal a pseudogap behavior below T_{p}∼60 K in two kinds of layered FeSe-based superconductors with quasi2D nature. In the pseudogap regime, a weak diamagnetic signal and a remarkable Nernst effect are also observed, which indicates that the observed pseudogap behavior is related to superconducting fluctuations. These works confirm that strong phase fluctuation is an important character in the 2D iron-based superconductors as widely observed in high-T_{c} cuprate superconductors.

Development of a multi-color gas puff imaging diagnostic on HL-2A tokamak.

A Multi-Color (MC) gas puff imaging diagnostic has been developed on HL-2A tokamak. This diagnostic can simultaneously measure two-dimensional (2D, radial, and poloidal) electron density and temperature distributions with a good spatial resolution of 2.5 × 2.5 mm2 and a temporal resolution of about 100 µs at best in edge plasmas. The 2D electron density and temperature distributions are inferred from the ratios of intensities of three different neutral helium emission lines; therefore, it is also referred to as helium beam probe or beam emission spectroscopy on thermal helium. A compact light splitter is used to split the inlet visible emission beam into four channels, and the specific neutral helium lines of the wavelengths λ1 = 587.6 nm, λ2 = 667.8 nm, λ3 = 706.5 nm, and λ4 = 728.1 nm are measured, respectively. This MC diagnostic has been experimentally tested and calibrated on a linear magnetic confinement device Peking University Plasma Test device, and the measured 2D electron density and temperature distributions are compared with the Langmuir probe measurements.

[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].

Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 µg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.

[Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China].

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient's medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.